We have previously shown that transdermal nitroglycerin may induce an increase in the activity of the adrenergic and the renin-angiotensin-aldosterone systems (SRAA) in patients with chronic stable angina pectoris (SA); when the activation of these systems is more pronounced, the antianginal effect of this drug seems to be reduced. The aim of this study was to evaluate the antianginal efficacy of transdermal nitroglycerin administration (TTS-NG 10 mg.24 h-1) in combination with an ACE inhibitor without sulphydryl groups (BNZ, benazepril 10 mg b.i.d.) in respect to placebo, or to TTS-NG or BNZ administered as monotherapy. Twenty-four patients (21M, 3F) were admitted to this multicentre, randomized, double-blind, latin square, placebo-controlled study. Patients received all the treatments (placebo, TTS-NG, BNZ and BNZ + TTS-NG) each for one week; at the end of each week patients performed two exercise tests 2 and 22 h post-dosing. Two hours post-dosing, exercise duration at 1 mm ST depression was significantly increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05) treatments. Two hours post-dosing, exercise duration at peak exercise was also increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05); 22 h post-dosing the increase in exercise duration was significant only during TTS-NG + BNZ treatment (P < 0.05) in respect to placebo, but not during TTS-NG given alone. Rate-pressure product at 1 mm ST depression was significantly increased 2 h post-dosing during TTS-NG treatment (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Xamoterol, 200 mg b.d. was compared with digoxin 0·125 mg b.d. or t.d. in a 3-month double-blind trial in 178 patients with mild to moderate heart failure. Xamoterol and digoxin both significantly increased exercise duration, but greater changes were observed with xamoterol. Xamoterol also improved quality of life to a greater degree than digoxin, and was better tolerated.

A double-blind, crossover, randomized placebo controlled study involving 15 patients with effort stable angina, was carried out to assess atenolol (A) 100 mg during an 8-week period. Thereafter, atenolol antianginal efficacy was evaluated in a 6-month follow-up open non-comparative study. No antianginal drugs other than A were administered except for isosorbide dinitrate 5 mg when necessary. At the end of the 2-week wash-out period, and at the end of each 2-week period during the crossover phase of the study, and every 12 weeks during the 6-month follow-up, an ergometric test was performed and the following parameters were evaluated: HR, SBP, DP, Total Work Load (TWL) and S-T changes. The Barlett's test was performed to assess variance homogeneity, while the Tukey Hd test was used to evaluate the parameters during the treatments. During atenolol, the reduction in SBP was close to statistical significance, HR and S-T were significantly reduced (p less than or equal to 0.05) whereas TWL was significantly increased (p less than or equal to 0.05). During long-term atenolol treatment, all cardiovascular parameters clearly improved in comparison to the placebo period, confirming the antianginal efficacy of atenolol, even in the long-term treatment.

The efficacy of a 2.5 mg sustained-release buccal nitroglycerin preparation given 8-hourly in effort-induced stable angina pectoris was investigated by means of graded exercise testing in 15 patients. An initial double-blind crossover study, compared with a placebo (duration six days) was followed by a further 15-day open treatment period on the active drug. Exercise testing was carried out 2 and 7 h after tablet administration at the conclusion of active treatment in the double-blind phase, and 2 h after tablet administration at the conclusion of the open treatment phase. Workload and exercise duration were significantly increased and mean electrocardiographic ST segment depression and ST segment recovery time significantly reduced by buccal nitroglycerin in the initial phase of the study, and these improvements were maintained over the subsequent 15-day assessment period. Systolic blood pressure at rest was significantly decreased by active treatment; other haemodynamic parameters remained unchanged. The study demonstrated the efficacy of sustained-release buccal nitroglycerin in effort-induced stable angina pectoris, and an absence of (+) tolerance to the therapeutic effects of this mode of nitrate administration.

The authors relate their own experience with 24 hr Holter monitoring in course of cardiac rehabilitation after coronary bypass surgery as well as after valvular replacement. As regards patients after coronary surgery they report the experience they got in the evaluation of heart rate trend and cardiac arrhythmias as well as in silent ischemia study. About this last problem 116 patients with signs of ischemia both in stress test and in Holter recording are considered out of 491 who had undergone coronary surgery. Ischemia during 24 hr Holter monitoring develops at an heart rate lower than effort ischemia. Holter monitoring proves to be very useful also in patients after valvular replacement to study arrhythmias and to check drugs' efficacy. After displaying the results concerning arrhythmias of 24 hr Holter electrocardiograms recorded in 207 randomized patients who had undergone valvular replacement 15 days before, the authors dwell upon the use of Holter electrocardiography in 82 valvular patients after pharmacological cardioversion and show that major arrhythmias get a clear reduction thanks to rehabilitation.

The first approach to treatment of dyslipidaemia is with diet. Currently, modified soybean protein is often included in the diet. A study was made of 32 patients with types IIa and IIb dyslipidaemia to see what changes in blood lipids could be induced by a simple low fat diet and a diet with modified soybean protein substituted for part of the animal protein. After six weeks on the initial low fat diet, all of the patients had lower total cholesterol and triglyceride levels, but there were no significant changes in the high density lipoprotein-cholesterol levels. The same diet was continued for eight weeks by 19 of the patients, who continued to improve. The 13 patients who had shown the least response to the initial simple low protein diet were given a diet in which the animal protein was partially replaced with modified soybean protein. This diet further decreased the total cholesterol.

The effectiveness of Nitroderm TTS 5 and Nitroderm TTS 10 in stable effort-induced angina pectoris was assessed by measuring the tolerance of 20 selected in-patients to cycloergometric symptom-limited tests. During the week preceding the trial previous anti-anginal treatment was gradually withdrawn except for short-acting nitrates. Patients were also familiarized with ergometric laboratory environment. The trial started with a 24-h control period when placebo was given single-blind to each patient. A double-blind cross-over design was then followed, two groups of 10 patients each being subjected successively to two sequences of therapy. By means of the double-dummy technique, Nitroderm TTS 5 or Nitroderm TTS 10 and matching placebos were applied simultaneously once daily for 24 h on two different days. Resting heart rate and blood pressure were measured before starting each exercise test, which was performed 3 h after placebo as well as 3 and 24 h after Nitroderm TTS application. The results of the tests were evaluated in terms of maximum workload, duration of exercise and total work performed for each of the two doses administered and compared with the corresponding baseline values. When compared with placebo both Nitroderm TTS doses produced a significant change (P less than 0.01) in the assessment variables. After application of the active treatment, duration of exercise, total work performed and maximal workload were increased while lying and standing blood pressures were decreased. There was no significant difference between the two doses of Nitroderm TTS in the assessment variables, except for systolic blood pressure and lying heart rate 3 and 24 h, respectively, post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

The present investigation was undertaken to evaluate the effects of Dilazep, a new antiplatelet and coronary dilating drug, on the exercise tolerance of patients who had suffered previous myocardial infarction and were participating in a cardiac rehabilitation programme. Seventy-two patients were enrolled in the study. They were randomly allocated to two groups of 36 subjects; patients in group A took Dilazep, 300 mg daily; patients in group B took acetylsalicylic acid, 100 mg daily, or dipyridamole, 300 mg daily. Before and after treatment all patients underwent two maximal or symptom limited cycloergometer stress tests, respectively 30 and 60 days after the episode of acute myocardial infarction. Total exercise time, maximum workload reached, heart rate, blood pressure, double product and oxygen pulse were measured. In both groups a significant increase in both total exercise time and maximum workload reached was recorded at the second stress test; this may reflect a greater degree of physical conditioning due to the rehabilitation programme. In group A patients total exercise time increased from 457.12 +/- 5.36 sec to 588.28 +/- 8.24 sec (p less than 0.005), in group B patients it increased from 459.18 +/- 6.11 sec to 547.43 +/- 7.47 sec (p less than 0.005). The mean values of maximum workload reached increased in group A from 4512.14 +/- 116.47 kgm to 5288.57 +/- 145.38 kgm (p less than 0.005), and in group B from 4522.22 +/- 108.42 kgm to 5098 +/- 137.51 kgm (p less than 0.005). Thus the exercise tolerance improved more in patients taking Dilazep than in those taking acetylsalicylic acid or dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)